Antimicrobial activities and action mechanism studies of transportan 10 and its analogues against multidrug-resistant bacteria

doi:10.1002/psc.2781

CORC > 兰州大学 > 兰州大学 > 基础医学院 > 会议论文

	Antimicrobial activities and action mechanism studies of transportan 10 and its analogues against multidrug-resistant bacteria
	Xie, JQ; Gou, YM; Zhao, Q; Li, SS; Zhang, W; Song, JJ; Mou, LY; Li, JY; Wang, KR; Zhang, BZ
	2015-07
会议日期	JUN 30-JUL 04, 2014
会议地点	Datong City, PEOPLES R CHINA
关键词	Multidrug-resistant Bacteria Cell-penetrating Peptides Transportan 10 Structure-activity Relationships Action Mechanism
卷号	21
期号	7
DOI	10.1002/psc.2781
页码	599-607
英文摘要	The increased emergence of multidrug-resistant bacteria is perceived as a critical public health threat, creating an urgent need for the development of novel classes of antimicrobials. Cell-penetrating peptides that share common features with antimicrobial peptides have been found to have antimicrobial activity and are currently being considered as potential alternatives to antibiotics. Transportan 10 is a chimeric cell-penetrating peptide that has been reported to transport biologically relevant cargoes into mammalian cells and cause damage to microbial membranes. In this study, we designed a series of TP10 analogues and studied their structure-activity relationships. We first evaluated the antimicrobial activities of these compounds against multidrug-resistant bacteria, which are responsible for most nosocomial infections. Our results showed that several of these compounds had potent antimicrobial and biofilm-inhibiting activities. We also measured the toxicity of these compounds, finding that Lys substitution could increase the antimicrobial activity but significantly enhanced the cytotoxicity. Pro introduction could reduce the cytotoxicity but disrupted the helical structure, resulting in a loss of activity. In the mechanistic studies, TP10 killed bacteria by membrane-active and DNA-binding activities. In conclusion, TP10 and its analogues could be developed into promising antibiotic candidates for the treatment of infections caused by multidrug-resistant bacteria. Copyright (c) 2015 European Peptide Society and John Wiley & Sons, Ltd.
项目编号	National Natural Science Foundation of China [91213302, 81302798, 81473095] ; Key National S&T Program 'Major New Drug Development' of the Ministry of Science and Technology [2012ZX09504001-003] ; Program for Changjiang Scholars and Innovative Research Team in University [PCSIRT: IRT1137] ; Research Fund for the Doctoral Program of Higher Education of China [20130211130005] ; Innovation Group in Gansu Province [1210RJIA002] ; Fundamental Research Funds for the Central Universities [lzujbky-2014-143]
会议录	JOURNAL OF PEPTIDE SCIENCE
资助机构	NSFC ; NSFC ; MOST ; MOST ; MOE ; MOE ; LZU ; LZU ; GSSTD ; GSSTD ; NSFC ; NSFC ; MOST ; MOST ; MOE ; MOE ; LZU ; LZU ; GSSTD ; GSSTD
会议录出版地	HOBOKEN
学科主题	Biochemistry & Molecular Biology ; Chemistry
语种	英语
资助项目	国家自然科学基金项目 ; 国家科技重大专项 ; 长江学者和创新团队发展计划 ; 高等学校博士学科点专项科研基金 ; 中央高校基本科研业务费专项资金 ; 甘肃省创新研究群体计划
ISSN号	1075-2617
WOS记录号	WOS:000356813900012
内容类型	会议论文
源URL	[http://ir.lzu.edu.cn/handle/262010/183021]
专题	基础医学院_会议论文
通讯作者	Wang, R (reprint author), Lanzhou Univ, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, 222 Tian Shui South Rd, Lanzhou 730000, Peoples R China.
推荐引用方式 GB/T 7714	Xie, JQ,Gou, YM,Zhao, Q,et al. Antimicrobial activities and action mechanism studies of transportan 10 and its analogues against multidrug-resistant bacteria[C]. 见:. Datong City, PEOPLES R CHINA. JUN 30-JUL 04, 2014.